Carbon nanotubes have shown great potential in the biomedical field, particularly in areas of tissue engineering, thermal ablation (photo-thermal and photo-acoustic therapy) and in the development of drug release systems. This last application has permitted developing controlled and directed release systems of different drugs that range from small molecules to peptides and antibodies; these systems permit increasing the pharmacological activity of the drugs and diminishing the collateral effects associated to them due, in part, to the effect of permeability and retention that permits accumulating these nano-compounds in tumor tissues, and the pin shape of the nanotubes that facilitates penetration through these membranes and intra-cellular accumulation of the drug (Wong, B. S., et al., Advanced Drug Delivery Reviews 65 (2013):1964-2015).
Functionalization of the nanotubes permits improving solubility in aqueous media, reducing cytotoxicity, and generating additional sites to add other molecules for the purpose of bio-redirecting or imaging (Kesharwani, P., et al., Drug Discovery Today 17 (2012):1023-1030). This functionalization can be covalent by modifying the nanotube structure with hydrophilic functional groups or non-covalent by coating with macromolecules, like lipids, polymers, or surfactants (Wong, B. S., et al., Advanced Drug Delivery Reviews 65 (2013) 1964-2015).
In the field of chemotherapy, different nano-compounds have been evaluated for release of cytotoxic drugs, for example, multilayered nanotubes functionalized with triethylene glycol diamine or PVA and loaded with camptothecin, mono-layered nanotubes functionalized with PEG or folic acid conjugated to chitosan and loaded with doxorubicin.
Other documents revealed by the state-of-the-art and related to nano-compounds for drug release are discussed ahead:
Patent Application Publication No. US2010209479 reveals a composition for cancer treatment that comprises a multilayered carbon nanotube and at least one therapeutic agent disposed within the nanotube, where the nanotube has a length between 500 nm and 2 μm and is coated with a polymer material selected from alginate, PLGA, polylactic acid, polydecanodiol citrate, and combinations of the same. Where the therapeutic agent is selected from xaliplatin and mitomycin and is present in a concentration between 1 and 300 μM. The patent reveals a treatment method that comprises placing said composition in contact with cancerous tissue and accelerating the reuptake of the therapeutic agent through localized irradiation with electromagnetic radiation for a time below 10 seconds.
Document US2007202334 reveals a nanomaterial that comprises anatase phase titanium dioxide in Nano fiber form with a length of at least 2 μm and diameter between 0.5 and 3 nm. Said nanofiber comprises at least a doping metal or non-metal selected from calcium, cobalt, nickel, copper, gallium, strontium, zirconium, palladium, silver, platinum, boron, carbon, nitrogen, sulfur, or fluorine among others. Likewise, the document reveals a catalytic composition that comprises anatase phase titanium dioxide nanoparticles, which in combination with irradiation of visible light reduce the percentage of organic substance or the viability of bacteria.
Document US2014155333 divulges a method for cancer treatment that comprises administration of: (a) a carbon nanotube-protein complex, where said nanotube is single-wall type (SWNT) semiconductor and non-metallic, where the protein or peptide is bonded to the SWNT through a derivate of the cellulose and is capable of recognizing a receptor of an ion of the endothelial tumor vasculature or of the external surface of these tumor cells; (b) electromagnetic radiation in a wavelength absorbable by the SWNT that generates increased temperature of the nanotube-protein complex and causes damage or death of said tumor cell.
In spite of the development of different nano-compounds, both single- and multi-layered, which incorporate drugs or proteins in their interior or bonded to the surface that permit increasing cytotoxicity and diminishing collateral effects, the need exists to develop new selective cytotoxic nano-compounds that in co-treatment with ionizing radiations permit eliminating tumor cells without the deleterious effects of the chemo and/or conventional radiotherapy on non-tumor cells. The nano-compounds of the present invention that comprises functionalized multi-walled carbon nanotubes with groups and Anatase phase TiO2 (TiO2-FMWCNTs) and functionalized multi-walled carbon nanotubes, Anatase phase TiO2 and folate (TiO2-FMWNTs-Folate) are cytotoxic against tumor cells, while not inducing cytotoxic effects upon normal cells; are not genotoxic or mutagenic and in combination with UV-A-type radiation increase cytotoxicity against tumor cells becoming an alternative to solving the errors of the nano-compounds divulged previously.